Several important advances have been made during the last year of study on this project. 1) A novel type of pneumococcal tolerant mutant (LYT plus TOL plus) has been isolated. These bacteria have normal penicillin binding proteins (PBP) and, apparently, normal levels of autolytic activities, yet, penicillin-treatment cannot induce lysis of the mutants. 2) Penicillin tolerant mutants, relatively resistant to the killing action of penicillin, have been isolated in group A streptococci. 3) The rapid killing effect of penicillin in group A streptococci can not be explained by a unique irreversibility of the interaction between PBPs and penicillin. 4) Aminoglycosides stimulate the in vivo degradation of PBPs. 5) Acidic pH, generated during culture growth, protects group B streptococci against the bactericidal effect of penicillin. However, such bacteria can still be "sensitized" (by penicillin) to the bactericidal effect on human white blood cells (PMN). Studies are planned to expand these observations along the lines of the original research proposal.